Department of Health Sciences, University of Genoa, 16132 Genoa, Italy.
IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy.
Theranostics. 2018 Mar 8;8(8):2147-2160. doi: 10.7150/thno.22726. eCollection 2018.
: MicroRNAs are small non-coding RNAs that regulate gene expression, thereby playing a role in a variety of physiological and pathophysiological states. Exposure to cigarette smoke extensively downregulates microRNA expression in pulmonary cells of mice, rats, and humans. Cellular microRNAs are released into body fluids, but a poor parallelism was previously observed between lung microRNAs and circulating microRNAs. The purpose of the present study was to validate the application of this epigenetic biomarker by using less invasive collection procedures. : Using microarray analyses, we measured 1135 microRNAs in 10 organs and 3 body fluids of mice that were either unexposed or exposed to mainstream cigarette smoke for up to 8 weeks. The results obtained with selected miRNAs were validated by qPCR. : The lung was the main target affected by smoke (190 dysregulated miRNAs), followed by skeletal muscle (180), liver (138), blood serum (109), kidney (96), spleen (89), stomach (36), heart (33), bronchoalveolar lavage fluid (32), urine (27), urinary bladder (12), colon (5), and brain (0). Skeletal muscle, kidney, and lung were the most important sources of smoke-altered microRNAs in blood serum, urine, and bronchoalveolar lavage fluid, respectively. : microRNA expression analysis was able to identify target organs after just 8 weeks of exposure to smoke, well before the occurrence of any detectable histopathological alteration. The present translational study validates the use of body fluid microRNAs as biomarkers applicable to human biomonitoring for mechanistic studies, diagnostic purposes, preventive medicine, and therapeutic strategies.
: 微小 RNA 是一类小的非编码 RNA，可调节基因表达，从而在多种生理和病理生理状态中发挥作用。香烟烟雾暴露会广泛地下调小鼠、大鼠和人类肺部细胞中的微小 RNA 表达。细胞微小 RNA 会被释放到体液中，但以前观察到肺微小 RNA 与循环微小 RNA 之间存在较差的平行关系。本研究的目的是通过使用微创采集程序来验证这种表观遗传生物标志物的应用。: 我们使用微阵列分析测量了未暴露或暴露于主流香烟烟雾长达 8 周的小鼠 10 个器官和 3 种体液中的 1135 个微小 RNA。通过 qPCR 验证了所选微小 RNA 的结果。: 肺部是受烟雾影响最大的主要靶器官（190 个失调的微小 RNA），其次是骨骼肌（180 个）、肝脏（138 个）、血清（109 个）、肾脏（96 个）、脾脏（89 个）、胃（36 个）、心脏（33 个）、支气管肺泡灌洗液（32 个）、尿液（27 个）、膀胱（12 个）、结肠（5 个）和大脑（0 个）。骨骼肌、肾脏和肺部分别是血清、尿液和支气管肺泡灌洗液中受烟雾影响的微小 RNA 的最重要来源。: 微小 RNA 表达分析能够在暴露于烟雾仅 8 周后识别出靶器官，远早于发生任何可检测的组织病理学改变之前。本转化研究验证了体液微小 RNA 作为生物标志物的应用，适用于机制研究、诊断目的、预防医学和治疗策略中的人体生物监测。
